The present invention relates to “active implantable medical devices” as defined by the 20 Jun. 1990 Directive 90/385/EEC of the Council of the European Communities, and more particularly to those devices that continuously monitor a patient's heart rhythm and deliver to the heart, if necessary, electrical pulses for joint and permanent stimulation of the left and the right ventricles, so as to resynchronize them, said technique being known as Cardiac Resynchronization Therapy (“CRT”) or Bi-Ventricular Pacing (“BVP”).
Cardiac resynchronization is known whereby a patient is implanted with a device equipped with electrodes to stimulate various sites in both ventricles (often called a CRT device or CRT pacemaker). The CRT device typically applies between the respective moments of stimulation of the left and right ventricles a delay that is called an “interventricular delay” (VVD) which VVD is adjusted to resynchronize the contraction of both ventricles to optimize the patient's hemodynamic status.
A CRT pacemaker is for example disclosed in EP 1108446 A1 and its counterpart U.S. Pat. No. 6,556,866 (both assigned to Sorin CRM S.A.S., previously known as ELA Medical), which describes a CRT device for applying between the two ventricular pacing sites a variable VVD, adjusted to resynchronize the contractions of the ventricles with a fine optimization of the patient's hemodynamic status. The VVD may be zero (meaning that the left and right ventricles are stimulated essentially simultaneously), positive (meaning that the left ventricle is stimulated after the right ventricle) or negative (meaning that the right ventricle is stimulated after the left ventricle).
Clinical studies have often observed a dramatic improvement in results for patients diagnosed with heart failure that is not improved by conventional therapy, because the parameters of the CRT therapy have been precisely adjusted according to the patient and to the nature of the patient's disorder.
But the implementation of CRT devices remains a very delicate intervention for the practitioner, because of the many choices that must be made. First, it must be determined for each of the leads the best stimulation site. The physical locations of the pacing electrodes for each lead relative to the myocardial tissue are called “pacing sites”; generally, these pacing sites can only be selected at implantation, by appropriate positioning of the electrodes. It is important to verify the effectiveness of the selected pacing sites, due to the possible influence of long-term efficacy of the resynchronization therapy. In some cases, the CRT device has several multi-site electrodes placed in the same cavity, and a change of pacing site(s) for delivering stimulation pulses in this cavity is possible by internal switching of the device.
In any case, during the intervention, the practitioner tests several possible pacing sites by successive repositioning of the lead to find the one that he believes is the most appropriate.
Another aspect of the development of these CRT devices is the increasing number of electrodes, especially for “multisite” devices that allow selecting the pacing sites used for the delivery of stimulation pulses and detection of myocardial potentials (e.g., from spontaneous cardiac events) and optimizing the operation of the CRT device.
The increasing number of electrodes can also result from the presence at the same level of the lead of several sectorial electrodes (electrodes specifically directed in a radial direction relative to the lead, at the pacing site), with the possibility to select one or the other of these sectorial electrodes to optimize the delivery of pulses to the selected pacing site. This is particularly true for leads implanted in the coronary venous system, for indirect stimulation of a left cavity: with several sectorial electrodes, it is possible to select one that is turned towards the epicardium wall facing the cavity in contact with this wall.
Second, with the development of implantable medical devices for stimulation of more than two ventricular sites, it is necessary to determine whether this *** “tri-ventricular” or “multi-ventricular” mode of stimulation is or is not preferable to a conventional “bi-ventricular” pacing mode.
Thus, the practitioner may be faced with a choice between a standard mode of bi-ventricular pacing (right and left ventricles), a tri-ventricular pacing mode (simultaneous stimulation by three electrodes, with an additional electrode in the right or left cavity), or even multi-ventricular (with multi-electrode leads for which multiple electrodes of the same lead are used concurrently). By appropriate switching, the practitioner can choose the most appropriate stimulation mode, but the number of possible configurations increases very rapidly with the increase of the electrodes, making the task all the more difficult for the practitioner, faced with a choice between a large number of different configurations.
Third, the device should be set properly, including the atrioventricular delay (AVD) and interventricular delay (VVD).
The many opportunities arising from these various choices are referred to as “pacing configurations.”
Indeed, it appears that today, even with full implementation of procedures, there are approximately 30% of patients who do not respond to CRT therapy, with serious consequences that can be imagined in terms of quality of life, hospitalizations for heart failure and reduced life expectancy.
Most studies now focus on methods to treat this refractory patient population by testing new stimulation configurations, and seeking to optimize the stimulation setting, during the implantation as well as on an ongoing basis, by periodic reassessments.
There is thus a real need for a technique to evaluate, according to a simple, rapid, automated and precise method, the impact of the choice of the stimulation sites and of the parameters of CRT therapy, especially the AVD and VVD, so as to optimize the patient's hemodynamic status.
The reference technique for the adjustment of CRT stimulation parameters is an assessment by echocardiography with estimation of the characteristic delays of the systole, in particular the delay of opening of the aortic valve. This procedure, which must be implemented in hospitals and by qualified personnel, is time consuming and expensive and cannot be applied as often as would be useful or necessary. In addition, it is not easy to perform ultrasound measurements during the implantation procedure, as the sterile field does not allow easy access to the patient's chest with the ultrasound probe.
Other techniques have been proposed to evaluate the effectiveness of the choice of stimulation pacing sites and of the setting of CRT therapy parameters. Thus, EP 1736203 A1 and its US counterpart U.S. Pat. No. 7,664,547 (both assigned to Sorin CRM S.A.S, previously known as ELA Medical) describe a CRT device that uses for this purpose the parameters related to endocardial acceleration (hereinafter “EA”) to determine an optimal pacing configuration, at the time of implantation or thereafter.
Indeed, it may be necessary to reassess these choices later, after the initial implantation, and eventually readjust the settings. The benefits provided by CRT therapy can ultimately lead to change the initial configuration and setup of the stimulation.
Indeed, several clinical studies have shown that endocardial acceleration is a parameter that accurately and in real-time reflects phenomena related to the movements of the heart chamber, and can therefore provide comprehensive information on the mechanical heart, both in the case of normal operation and in the case of a deficient operation. Endocardial acceleration is for example measured by an accelerometer integrated into an endocardial lead, as described for example in EP 0515319 A1 and its US counterpart U.S. Pat. No. 5,304,208 (both assigned to Sorin Biomedica Cardio SpA).
WO 2006/049538 A1 (St. Jude Medical AB) describes a known technique to evaluate a physiological parameter that reflects the hemodynamic performance of the heart for a given stimulation configuration, from various sensors (pressure, acceleration, acoustic) placed on one or more leads, some of them being possibly repositioned; thus the signal delivered by these sensors depends on the current position of the lead and cannot be a reliable reference. However, the proposed technique has a number of drawbacks, including the fact that the optimization is based on the analysis of a single physiological parameter (e.g., cardiac output, stroke volume). However, some patients may be more or less sensitive to either of these parameters, which is not always the same from one patient to another because of the specific response of the patient, his pathology and the evolution of it. Further, the analyzed parameter is not necessarily the most relevant relatively to the changes in the stimulation configuration.